Multilayer coating for releasing biologically-active agents and method of making

• US 20060216327A1
• Filed: 03/28/2005
• Published: 09/28/2006
• Est. Priority Date: 03/28/2005
• Status: Abandoned Application

• Current Assignee: Bacterin International Incorporated (OrbiMed Advisors LLC (China))
• Original Assignee: Bacterin International Incorporated (OrbiMed Advisors LLC (China))
• Inventors: Madsen, Todd A., Yanaki, Jamal S.
• Application Number:
  US11/091,354
• Publication Number:
  US 20060216327A1
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61L 2300/402 Anaestetics, analgesics, e.g. lidocaine
• CPC Class Codes: A61L 2300/61 containing two or more active agents in different layers
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

A composition for use with healthcare products such as medical device includes one or more biologically-active agents for release into bodily fluids. The composition can be applied to a substrate to form an erodible layer and a polymer layer. Biologically-active agent(s) are releasable from the erodible layer and the polymer layer when exposed to aqueous fluids.

Claims

1. An article capable of affecting a biological process, the article comprising:

a substrate having a surface;

an erodible layer positioned over the surface of the substrate and comprising a release material and a first biologically-active agent releasable from the erodible layer when exposed to an aqueous fluid; and

a polymer layer comprising a polymer and a second biologically-active agent releasable from the polymer layer when exposed to the aqueous fluid.

2. The article of claim 1, wherein the first and second biologically-active agents are the same biologically-active agent.

3. The article of claim 1, wherein the release material is selected from the group consisting of inorganic crystalline materials, inorganic amorphous materials, organic crystalline materials, and organic amorphous materials.

4. The article of claim 1, wherein the release material is selected from the group consisting of calcium phosphate and calcium sulfate.

5. The article of claim 1, wherein the polymer is selected from the group consisting of hydrophilic polymers, hydrophobic polymers, and polysaccharides.

6. The article of claim 1, wherein the first and second biologically-active agents are selected from the group consisting of analgesics, antimicrobials, anti-inflammatories, targeting agents, cytokines, immunotoxins, antihistamines, receptor-binding agents, chemotherapeutics, growth factors, immunoglobulins, pharmaceuticals, nutraceuticals, antithrombogenic agents, antitumor agents, antiangiogenic agents, anesthetics, vasodilation substances, wound healing agents, diagnostic agents, and any combination of these.

7. The article of claim 1, wherein the article is configured to release the second biologically-active agent, upon exposure to the aqueous fluid, more rapidly than the first biologically-active agent.

8. The article of claim 1, wherein release kinetics of the first biologically-active agent depends on a rate of erosion of the erodible layer when exposed to the aqueous fluid.

9. The article of claim 1, wherein release kinetics of the second biologically-active agent depends on a rate of diffusion of the second biologically-active agent.

10. The article of claim 1, wherein the surface of the substrate includes functional groups that function as attachment sites for the erodible layer.

11. The article of claim 1, wherein the polymer layer mechanically reinforces the erodible layer.

12. The article of claim 1, wherein the erodible layer is in contact with polymer layer.

13. The article of claim 1, wherein the erodible layer is in contact with the substrate surface.

14. A composition for affecting a biological process, the composition comprising:

a release material that disintegrates in an aqueous fluid;

a first biologically-active agent incorporated within the release material and releasable through disintegration of the release material;

a polymer matrix; and

a second-biologically active agent incorporated within the polymer matrix and releasable from the polymer matrix upon exposure to an aqueous fluid.

15. The composition of claim 14, wherein the first biologically-active agent is releasable from the release material with substantially zero-order release kinetics.

16. The composition of claim 14, wherein the second biologically-active agent is releasable from the polymer matrix with substantially first-order release kinetics.

17. The composition of claim 14, wherein the second biologically-active agent is releasable from the polymer matrix with substantially second-order release kinetics.

18. The composition of claim 14, wherein the composition is configured to release, upon exposure to the aqueous fluid, the second biologically-active agent more rapidly than the first biologically-active agent.

19. The composition of claim 14, wherein the first and second biologically-active agents are the same biologically-active agent.

20. The composition of claim 14, wherein the release material is selected from the group consisting of inorganic crystalline materials, inorganic amorphous materials, organic crystalline materials, and organic amorphous materials.

21. The composition of claim 14, wherein the release material is selected from the group consisting of calcium phosphate and calcium sulfate.

22. The composition of claim 14, wherein the first and second biologically-active agents are selected from the group consisting of analgesics, antimicrobials, anti-inflammatories, targeting agents, cytokines, immunotoxins, antihistamines, receptor-binding agents, chemotherapeutics, growth factors, immunoglobulins, pharmaceuticals, nutraceuticals, antithrombogenic agents, antitumor agents, antiangiogenic agents, anesthetics, vasodilation substances, wound healing agents, diagnostic agents, and any combination of these.

23. The composition of claim 14, wherein the polymer matrix is in contact with the release material.

24. A method for coating a substrate, the method comprising:

providing functional groups on a surface of the substrate;

depositing a base layer on the functionalized surface, the base layer comprising;

a release material; and

a first biologically-active agent; and

forming a polymer layer over the base layer, the polymer layer including a second biologically-active agent that is releasable from the polymer layer when exposed to an aqueous fluid.

25. The method of claim 24, wherein the first and second biologically active-agents are the same biologically-active agent.

26. The method of claim 24, wherein, after the polymer layer is formed over the base layer, the polymer layer is immersed in a solution including the second-biologically active agent.

27. The method of claim 24, and further comprising:

mixing the second biologically-active agent and the polymer before forming the polymer layer over the base layer.

28. The method of claim 24, wherein the first and second biologically-active agents are selected from the group consisting of analgesics, antimicrobials, anti-inflammatories, targeting agents, cytokines, immunotoxins, antihistamines, receptor-binding agents, chemotherapeutics, growth factors, immunoglobulins, pharmaceuticals, nutraceuticals, antithrombogenic agents, antitumor agents, antiangiogenic agents, anesthetics, vasodilation substances, wound healing agents, diagnostic agents, and any combination of these.

29. The method of claim 24, wherein depositing a base layer comprises immersing the functionalized surface of the substrate in a coating solution including the release material and the first-biologically-active agent.

30. The method of claim 24, wherein the polymer layer is in contact with the base layer.